Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure
Abstract Aims We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). Methods and results In the first stage, 83 HF‐related left ventricular (LV) transcripts were examined in patients with...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-12-01
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| Series: | ESC Heart Failure |
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| Online Access: | https://doi.org/10.1002/ehf2.13659 |
| _version_ | 1828346625506934784 |
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| author | Leen Delrue Marc Vanderheyden Monika Beles Pasquale Paolisso Giuseppe Di Gioia Riet Dierckx Sofie Verstreken Marc Goethals Ward Heggermont Jozef Bartunek |
| author_facet | Leen Delrue Marc Vanderheyden Monika Beles Pasquale Paolisso Giuseppe Di Gioia Riet Dierckx Sofie Verstreken Marc Goethals Ward Heggermont Jozef Bartunek |
| author_sort | Leen Delrue |
| collection | DOAJ |
| description | Abstract Aims We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). Methods and results In the first stage, 83 HF‐related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age‐matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up‐regulated in non‐survivors vs. survivors (2.40 ± 3.66 vs. 0.36 ± 0.22 units, P < 0.01 and 334.7 ± 138.7 vs. 228.2 ± 83.1 μg/mL, P < 0.01, respectively). While no significant transmyocardial gradient was detected, cytokine stimulation of human endothelial cells induced SERPINA3 secretion. In an independent validation cohort with a de novo or worsened HF (n = 387), circulating SERPINA3 levels > 316 μg/mL were associated with increased all‐cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5–3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2–3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N‐terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all‐cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure. Conclusion In patients with a de novo or worsened HF, increased SERPINA3 levels > 316 μg/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF. |
| first_indexed | 2024-04-14T00:29:01Z |
| format | Article |
| id | doaj.art-2dd42a98df5e4d9dace59bc79f9d21dd |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-04-14T00:29:01Z |
| publishDate | 2021-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-2dd42a98df5e4d9dace59bc79f9d21dd2022-12-22T02:22:36ZengWileyESC Heart Failure2055-58222021-12-01864780479010.1002/ehf2.13659Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failureLeen Delrue0Marc Vanderheyden1Monika Beles2Pasquale Paolisso3Giuseppe Di Gioia4Riet Dierckx5Sofie Verstreken6Marc Goethals7Ward Heggermont8Jozef Bartunek9Cardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumCardiovascular Center OLV Hospital Moorselbaan 164 Aalst 9300 BelgiumAbstract Aims We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). Methods and results In the first stage, 83 HF‐related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age‐matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up‐regulated in non‐survivors vs. survivors (2.40 ± 3.66 vs. 0.36 ± 0.22 units, P < 0.01 and 334.7 ± 138.7 vs. 228.2 ± 83.1 μg/mL, P < 0.01, respectively). While no significant transmyocardial gradient was detected, cytokine stimulation of human endothelial cells induced SERPINA3 secretion. In an independent validation cohort with a de novo or worsened HF (n = 387), circulating SERPINA3 levels > 316 μg/mL were associated with increased all‐cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5–3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2–3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N‐terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all‐cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure. Conclusion In patients with a de novo or worsened HF, increased SERPINA3 levels > 316 μg/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF.https://doi.org/10.1002/ehf2.13659Heart failurePrognosisBiomarkersInflammationCardiomyopathy |
| spellingShingle | Leen Delrue Marc Vanderheyden Monika Beles Pasquale Paolisso Giuseppe Di Gioia Riet Dierckx Sofie Verstreken Marc Goethals Ward Heggermont Jozef Bartunek Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure ESC Heart Failure Heart failure Prognosis Biomarkers Inflammation Cardiomyopathy |
| title | Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure |
| title_full | Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure |
| title_fullStr | Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure |
| title_full_unstemmed | Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure |
| title_short | Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure |
| title_sort | circulating serpina3 improves prognostic stratification in patients with a de novo or worsened heart failure |
| topic | Heart failure Prognosis Biomarkers Inflammation Cardiomyopathy |
| url | https://doi.org/10.1002/ehf2.13659 |
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